Renal function alters the association of lipoprotein(a) with cardiovascular outcomes in patients undergoing percutaneous coronary intervention: a prospective cohort study.

Background and hypothesis: Lipoprotein(a) [Lp(a)] and renal dysfunction are both independent risk factors for cardiovascular disease. However, it remains unclear whether renal function mediates the association between Lp(a) and cardiovascular outcomes in patients undergoing percutaneous coronary intervention (PCI). Methods: From a large prospective cohort study, 10 435 eligible patients undergoing PCI from January 2013 to December 2013 were included in our analysis. Patients were stratified into three renal function groups according to their baseline estimated glomerular filtration rate (eGFR) (<60; 60-90; ≥90 ml/min/1.73 m2). The primary endpoint was a composite of all-cause death, nonfatal MI, ischemic stroke, and unplanned revascularization [major adverse cardiac and cerebrovascular events (MACCE)]. Results: Over a median follow-up of 5.1 years, a total of 2144 MACCE events occurred. After multivariable adjustment, either eGFR <60 ml/min/1.73 m2 or elevated Lp(a) conferred a significantly higher MACCE risk. Higher Lp(a) was significantly associated with an increased risk of MACCE in patients with eGFR <60 ml/min/1.73 m2. However, this association was weakened in subjects with only mild renal impairment and diminished in those with normal renal function. A significant interaction for MACCE between renal categories and Lp(a) was observed (P = 0.026). Patients with concomitant Lp(a) ≥30 mg/dl and eGFR <60 ml/min/1.73 m2 experienced worse cardiovascular outcomes compared with those without. Conclusion: The significant association between Lp(a) and cardiovascular outcomes was mediated by renal function in patients undergoing PCI. Lp(a)-associated risk was more pronounced in patients with worse renal function, suggesting close monitoring and aggressive management are needed in this population.

A review of mesoscopic modeling and constitutive equations of particle-reinforced metals matrix composites based on finite element method.

Particle reinforced metal matrix composite (PRMMCs) has a complex mesoscopic structure, and the addition of particles can strengthen the metal matrix, which makes the deformation and failure behavior of PRMMCs under load very complicated. The finite element method can quantitatively describe the effect of PRMMCs microstructure parameters on the macroscopic properties of materials, but the key is to establish a representative volume element(RVE) model that can reflect the real mechanical properties of materials. This paper reports and discusses on the construction methods of the RVE model of PRMMCs from three aspects: the geometric modeling of PRMMCs microstructure, the construction of the matrix constitutive equation based on PRMMCs reinforcement mechanism and the interface module. In the end, Abaqus and some of its secondary development functions are introduced.

Effect of ozone sterilization on controlling leaf mildew and gray mold tomato disease in a glasshouse and its influence on other growth parameters.

BACKGROUND: In order to explore the effect of ozone sterilization treatment on tomato disease control and increase fruit setting rate, this study took 906 pink fruit tomato as test material, used a small ozone generator to carry out ozone treatment single-factor test, and then selected orthogonal table to guide the ozone treatment combination. The effects of different ozone treatment concentration, ozone treatment duration and ozone treatment times on the growth, disease and fruit setting rate of potted tomato were analyzed. RESULTS: Different ozone treatment had effects on leaf mildew, gray mold and fruit setting rate of tomato. The influence degree of three factors on leaf mildew, gray mold and fruit setting rate was from large to small, a > b > c, a > c > b, b > a > c. A quadratic regression model was established with the control effect of tomato leaf mildew, gray mold and fruit setting rate as response values, and the optimal parameter combination was determined: The ozone treatment concentration was 0.0465 g kg-1, the ozone treatment time was 30 min, and the ozone treatment times were twice a week. In this case, the control efficiency of tomato leaf mildew was 95.02%, the control effect of gray mold was 99.49%, and the fruit setting rate was 76.5%. The test parameters were accurate and reliable. CONCLUSION: The ozone sterilization method proposed in this article is safe and green, and can provide theoretical support for the recovery and reconstruction of tomato disease in a glasshouse. © 2024 Society of Chemical Industry.

Research on the coupling coordination relationship between the digital economy and high-quality energy development: Evidence from China.

The deep integration of the digital economy and high-quality energy development is a vital breakthrough in promoting the digital transformation and upgrading of energy, and it is also a critical path to achieving green and low-carbon development. However, the degree of integration of the two has yet to be discovered. This article measures the coupling coordination degree of the digital economy and high-quality energy development using panel data from 30 provinces in China from 2013 to 2020, explores the spatiotemporal evolution characteristics of the coupling coordination degree, and further analyzes the driving factors of the coupling coordination degree. The results show that:(1) The coupling coordination degree shows an upward trend, but there are apparent gradient differences and spatial non-equilibrium features in the coupling coordination degree among provinces. (2) The coupling coordination degree shows a "parabolic" spatial trend of "high east and low west" in the east-west direction and an "inverted U-shaped" spatial trend in the north-south direction. (3) The center of gravity of the coupling coordination degree moves to the southwest, clustering in the northeast-southwest direction and showing a spreading trend in the southeast-northwest direction. (4) The coupling coordination degree has a significant positive spatial correlation, and the cold-hot spot gradually develops into a distribution pattern with the Yangtze River Delta in China as the agglomeration center. (5) Economic development, industrial structure, government behavior, environmental regulation, urbanization, technological innovation, and external openness significantly impact the coupling coordination degree. In addition, economic development and human capital have a positive spatial spillover effect on the coupling coordination degree. Urbanization level and technological innovation have a negative spatial spillover effect on the coupling coordination degree. Accordingly, to promote the coupling and interaction between the digital economy and high-quality energy development, the government should take effective measures in optimizing the industrial structure, scientifically promoting the urbanization process, and enhancing the scientific and technological innovation capacity.

Biodegradable reactive compatibilizers for efficient in-situ compatibilization of poly (lactic acid)/poly (butylene adipate-terephthalate) blends.

The wide application of fully biodegradable polylactic acid/polybutylene terephthalate (PLA/PBAT) blends in environmentally friendly packaging were limited because of poor compatibility. Normal compatibilizers suffer from poor thermal stability and non-biodegradability. In this work, epoxy copolymer (MDOG) with different molecular structures were made of 2-methylene-1, 3-dioxoheptane, and glycidyl methacrylate as raw materials by free radical copolymerization. MDOG copolymers have good biodegradability and a high thermal decomposition temperature of 361 °C. The chemical reaction of the epoxy groups in MDOG with PLA and PBAT during the melting reaction improved the interfacial bonding by decreasing the particle size of PBAT. Compared to the PLA/PBAT blends, the tensile strength and fracture toughness of PLA/PBAT/MDOG blends were enhanced to 34.6 MPa and 115.8 MJ/m3, which are 25 % and 81 % higher, respectively. As a result, this work offers new methods for developing thermally stable and biodegradable compatibilizers, which will hopefully promote the development of packaging industry.

"Baihui" (DU20)-penetrating "Qubin" (GB7) acupuncture on blood-brain barrier integrity in rat intracerebral hemorrhage models via the RhoA/ROCK II/MLC 2 signaling pathway.

BACKGROUND: Blocking the RhoA/ROCK II/MLC 2 (Ras homolog gene family member A/Rho kinase II/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke, cerebral ischemia, and subarachnoid hemorrhage. Nevertheless, it is not clear whether and how disrupting the RhoA/ROCK II/MLC 2 signaling pathway changes the pathogenic processes of the blood-brain barrier (BBB) after intracerebral hemorrhage (ICH). The present investigation included the injection of rat caudal vein blood into the basal ganglia area to replicate the pathophysiological conditions caused by ICH. METHODS: Scalp acupuncture (SA) therapy was performed on rats with ICH at the acupuncture point "Baihui"-penetrating "Qubin," and the ROCK selective inhibitor fasudil was used as a positive control to evaluate the inhibitory effect of acupuncture on the RhoA/ROCK II/MLC 2 signaling pathway. Post-assessments included neurological deficits, brain edema, Evans blue extravasation, Western blot, quantitative polymerase chain reaction, and transmission electron microscope imaging. RESULTS: We found that ROCK II acts as a promoter of the RhoA/ROCK II/MLC 2 signaling pathway, and its expression increased at 6 h after ICH, peaked at 3 days, and then decreased at 7 days after ICH, but was still higher than the pre-intervention level. According to some experimental results, although 3 days is the peak, 7 days is the best time point for acupuncture treatment. Starting from 6 h after ICH, the neurovascular structure and endothelial cell morphology around the hematoma began to change. Based on the changes in the promoter ROCK II, a 7-day time point was selected as the breakthrough point for treating ICH model rats in the main experiment. The results of this experiment showed that both SA at "Baihui"-penetrating "Qubin" and treatment with fasudil could improve the expression of endothelial-related proteins by inhibiting the RhoA/ROCK II/MLC 2 signaling pathway and reduce neurological dysfunction, brain edema, and BBB permeability in rats. CONCLUSION: This study found that these experimental data indicated that SA at "Baihui"-penetrating "Qubin" could preserve BBB integrity and neurological function recovery after ICH by inhibiting RhoA/ROCK II/MLC 2 signaling pathway activation and by regulating endothelial cell-related proteins.

Predictive value of serum MDA and 4-HNE levels on the occurrence of early neurological deterioration after intravenous thrombolysis with rt-PA IVT in patients with acute ischemic stroke.

OBJECTIVE: This study investigated the predictive value of serum MDA and 4-HNE levels on early neurological deterioration (END) after recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients. METHODS: This study analyzed 287 AIS patients with standard-dose rt-PA IVT. Clinical baseline and pathological data were recorded before rt-PA IVT, and neurologic deficit was assessed by NIHSS. AIS patients were classified into Non-END and END groups. Serum MDA and 4-HNE levels were determined by ELISA and their correlations with NIHSS scores were evaluated. AIS patients were allocated into groups with high and low MDA or 4-HNE expression, and post-IVT END incidence was compared. Independent risk indexes for post-IVT END and the predictive value of serum MDA+4-HNE levels on post-IVT END were assessed. RESULTS: Serum MDA and 4-HNE were higher in AIS patients with post-IVT END. NIHSS score showed a positive correlation with serum MDA and 4-HNE levels. MDA levels were positively correlated with 4-HNE levels in AIS patients. END after IVT was increased in AIS patients with high MDA/4-HNE expression. FBG, lymphocyte percentage, PLR, NIHSS score, serum MDA, and 4-HNE levels were independent risk factors for END after IVT. The diagnostic efficacy of MDA+4-HNE in assessing post-IVT END in AIS patients (sensitivity 92.00 %, specificity 82.70 %) was higher than MDA or 4-HNE alone. CONCLUSION: Serum MDA and 4-HNE levels were higher in AIS patients with post-IVT END than in those with non-END, and MDA+4-HNE possessed a higher predictive value for post-IVT END in AIS patients.

Implications of left atrial volume index in patients with three-vessel coronary disease: A 6.6-year follow-up cohort study.

BACKGROUND: Risk assessment and treatment stratification for three-vessel coronary disease (TVD) remain challenging. This study aimed to investigate the prognostic value of left atrial volume index (LAVI) with the Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score II, and its association with the long-term prognosis after three strategies (percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], and medical therapy [MT]) in patients with TVD. METHODS: This study was a post hoc analysis of a large, prospective cohort of patients with TVD in China, that aimed to determine the long-term outcomes after PCI, CABG, or optimal MT alone. A total of 8943 patients with TVD were consecutively enrolled between 2004 and 2011 at Fuwai Hospital. A total of 7818 patients with available baseline LAVI data were included in the study. Baseline, procedural, and follow-up data were collected. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which was a composite of all-cause death, myocardial infarction (MI), and stroke. Secondary endpoints included all-cause death, cardiac death, MI, revascularization, and stroke. Long-term outcomes were evaluated among LAVI quartile groups. RESULTS: During a median follow-up of 6.6 years, a higher LAVI was strongly associated with increased risk of MACCE (Q3: hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.06-1.37, P = 0.005; Q4: HR 1.85, 95%CI 1.64-2.09, P <0.001), all-cause death (Q3: HR 1.41, 95% CI 1.17-1.69, P <0.001; Q4: HR 2.54, 95%CI 2.16-3.00, P <0.001), and cardiac death (Q3: HR 1.81, 95% CI 1.39-2.37, P <0.001; Q4: HR 3.47, 95%CI 2.71-4.43, P <0.001). Moreover, LAVI significantly improved discrimination and reclassification of the SYNTAX score II. Notably, there was a significant interaction between LAVI quartiles and treatment strategies for MACCE. CABG was associated with lower risk of MACCE than MT alone, regardless of LAVI quartiles. Among patients in the fourth quartile, PCI was associated with significantly increased risk of cardiac death compared with CABG (HR: 5.25, 95% CI: 1.97-14.03, P = 0.001). CONCLUSIONS: LAVI is a potential index for risk stratification and therapeutic decision-making in patients with three-vessel coronary disease. CABG is associated with improved long-term outcomes compared with MT alone, regardless of LAVI quartiles. When LAVI is severely elevated, PCI is associated with higher risk of cardiac death than CABG.

Chondroitin Sulfate Proteoglycans Revisited: Its Mechanism of Generation and Action for Spinal Cord Injury.

Reactive astrocytes (RAs) produce chondroitin sulfate proteoglycans (CSPGs) in large quantities after spinal cord injury (SCI) and inhibit axon regeneration through the Rho-associated protein kinase (ROCK) pathway. However, the mechanism of producing CSPGs by RAs and their roles in other aspects are often overlooked. In recent years, novel generation mechanisms and functions of CSPGs have gradually emerged. Extracellular traps (ETs), a new recently discovered phenomenon in SCI, can promote secondary injury. ETs are released by neutrophils and microglia, which activate astrocytes to produce CSPGs after SCI. CSPGs inhibit axon regeneration and play an important role in regulating inflammation as well as cell migration and differentiation; some of these regulations are beneficial. The current review summarized the process of ET-activated RAs to generate CSPGs at the cellular signaling pathway level. Moreover, the roles of CSPGs in inhibiting axon regeneration, regulating inflammation, and regulating cell migration and differentiation were discussed. Finally, based on the above process, novel potential therapeutic targets were proposed to eliminate the adverse effects of CSPGs.

Telemedicine network latency management system in 5G telesurgery: a feasibility and effectiveness study.

BACKGROUND: Network latency is the most important factor affecting the performance of telemedicine. The aim of the study is to assess the feasibility and efficacy of a novel network latency management system in 5G telesurgery. METHODS: We conducted 20 telesurgery simulation trials (hitching rings to columns) and 15 remote adrenalectomy procedures in the 5G network environment. Telemedicine Network Latency Management System and the traditional "Ping command" method (gold standard) were used to monitor network latency during preoperative simulated telesurgery and formal telesurgery. We observed the working status of the Telemedicine Network Latency Management System and calculated the difference between the network latency data and packet loss rate detected by the two methods. In addition, due to the lower latency of the 5G network, we tested the alert function of the system using the 4G network with relatively high network latency. RESULTS: The Telemedicine Network Latency Management System showed no instability during telesurgery simulation trials and formal telesurgery. After 20 telesurgery simulation trials and 15 remote adrenalectomy procedures, the p-value for the difference between the network latency data monitored by the Telemedicine Network Latency Management System and the "Ping command" method was greater than 0.05 in each case. Meanwhile, the surgeons reported that the Telemedicine Network Latency Management System had a friendly interface and was easy to operate. Besides, when the network latency exceeded a set threshold, a rapid alarm sounded in the system. CONCLUSION: The Telemedicine Network Latency Management System was simple and easy to operate, and it was feasible and effective to use it to monitor network latency in telesurgery. The system had an intuitive and concise interface, and its alarm function increased the safety of telesurgery. The system's own multidimensional working ability and information storage capacity will be more suitable for telemedicine work.

Latencies to the first interictal epileptiform discharges recorded by the electroencephalography in different epileptic patients.

PURPOSE: Interictal epileptiform discharges (IEDs) captured in electroencephalography (EEG) have a high diagnostic value for epileptic patients. Extending the recording time may increase the possibility of obtaining IEDs. The purpose of our research was to determine how long it took for various epileptic individuals to receive their first IEDs. METHODS: We retrospectively analyzed patients who were diagnosed with epilepsy and had no anti-seizure medications (ASMs) between September 2018 and March 2019 in the neurology department of the First Affiliated Hospital of Xi'an Jiaotong University. Each individual underwent a 24-h long-term video electroencephalographic monitoring (VEM) procedure. Clinical information including age, gender, age of seizure onset, frequency of seizures, the interval between last seizure and VEM, and results of neuroimaging were gathered. We also calculated the times from the start of the VEM to the first definite IEDs. RESULTS: A total of 241 patients were examined, including 191 with focal-onset epilepsy and 50 with generalized epilepsy. In individuals with focal-onset epilepsy, the median latency to the first IED was 63.0 min (IQR 19.0-299.0 min), as compared to 30.0 min (IQR 12.5-62.0 min) in patients with generalized epilepsy (p < 0.001). The latency to the first IED is significantly related to the age of seizure onset (HR = 0.988, p = 0.049), the interval between last seizure and VEM (HR = 0.998, p = 0.013). But it is not correlated with seizure frequency, gender and age. CONCLUSIONS: IEDs were discovered during 24-h EEG monitoring in 222/241(92.1%) of the epilepsy patients that were included. Compared to focal-onset epilepsy, generalized epilepsy demonstrated a much shorter latency to IED. Patients with late-onset epilepsy or those without recent episodes may require longer EEG monitoring periods.

An elevated triglyceride-glucose index predicts adverse outcomes and interacts with the treatment strategy in patients with three-vessel disease.

BACKGROUND: Insulin resistance is a pivotal risk factor for cardiovascular diseases, and the triglyceride-glucose (TyG) index is a well-established surrogate of insulin resistance. This study aimed to investigate the prognostic value of the TyG index and its ability in therapy guidance in patients with three-vessel disease (TVD). METHODS: A total of 8862 patients with TVD with available baseline TyG index data were included in the study. The endpoint was major adverse cardiac events (MACE). All patients received coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or medical therapy (MT) alone reasonably. RESULTS: An elevated TyG index was defined as the TyG index greater than 9.51. During a median follow-up of 7.5 years, an elevated TyG index was significantly associated with an increased risk of MACE (adjusted hazard ratio 1.161, 95% confidence interval 1.026-1.314, p = 0.018). The elevated TyG index was shown to have a more pronounced predictive value for MACE in patients with diabetes, but failed to predict MACE among those without diabetes, whether they presented with stable angina pectoris (SAP) or acute coronary syndrome (ACS). Meanwhile, the association between an elevated TyG index and MACE was also found in patients with left main involvement. Notably, CABG conferred a significant survival advantage over PCI in patients with a normal TyG index, but was not observed to be superior to PCI in patients with an elevated TyG index unless the patients had both ACS and diabetes. In addition, the benefit was shown to be similar between MT and revascularisation among patients with SAP and an elevated TyG index. CONCLUSIONS: The TyG index is a potential indicator for risk stratification and therapeutic decision-making in patients with TVD.

Digital Support Systems to Improve Child Health and Development in Peru: Protocol for a Randomized Controlled Trial.

BACKGROUND: Children living in low and middle-income countries (LMICs) are at greater risk for experiencing adversities that can undermine their health and early development. Recently launched digital early childhood development (ECD) programs attempt to support families with young children in their home environments using digital technologies. However, relatively little is known regarding the effectiveness of these new technologies. OBJECTIVE: The goal of this study is to rigorously assess the reach, effectiveness, and cost-effectiveness of a newly developed digital ECD platform called Afini. The Afini platform was designed to support parents of young children in low-resource settings to improve ECD and interact with caregivers through messenger services and a chatbot. METHODS: This is a 3-arm cluster randomized controlled trial. In total, 2471 caregivers and their 3- to 9-month-old children were enrolled in the study across 164 study clusters in the San Marcos, Cajabamba, and Cajamarca provinces of Peru. Clusters of participants were randomly assigned to 1 of 3 groups: a control group (72 community clusters and 980 caregiver-child dyads), a home visit intervention group (20 community clusters and 316 caregiver-child dyads), and an Afini intervention group (72 community clusters and 1175 caregiver-child dyads). Families in the control group receive no focused ECD intervention. The home visit group is receiving biweekly home visits by a trained field staff following the national ECD program (Programa Nacional Cuna Más) curriculum and training guidelines. Caregivers in the Afini group are receiving ECD activities and advice through the digital platform. The primary study outcome is children's overall development at the age of 2.5 years, using the internationally validated long form of the Global Scales for Early Development. Secondary outcomes include caregiver engagement; caregiver mental health; screen time; as well as caregiver reports of children's motor, cognitive, language, and socioemotional development measured through locally piloted and validated tools. RESULTS: Enrollment started in September 2021 and ended in March 2023. Endline assessments will take place between August 2023 and September 2024. CONCLUSIONS: This study is, to our knowledge, the first to rigorously assess the effectiveness and cost-effectiveness of digital ECD technologies in LMICs. Given the large number of children in LMICs currently receiving only limited external support, the evaluated platform has the potential to improve the short- and long-term well-being of millions of children and their parents globally. TRIAL REGISTRATION: ClinicalTrials.gov NCT05202106; https://clinicaltrials.gov/ct2/show/NCT05202106. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50371.

Effect of Proinflammatory S100A9 Protein on Migration and Proliferation of Microglial Cells.

Alzheimer's disease (AD) is a multifactorial disease affecting aging population worldwide. Neuroinflammation became a focus of research as one of the major pathologic processes relating to the disease onset and progression. Proinflammatory S100A9 is the central culprit in the amyloid-neuroinflammatory cascade implicated in AD and other neurodegenerative diseases. We studied the effect of S100A9 on microglial BV-2 cell proliferation and migration. The responses of BV-2 cells to S100A9 stimulation were monitored in real-time using live cell microscopy, transcriptome sequencing, immunofluorescence staining, western blot analysis, and ELISA. We observed that a low dose of S100A9 promotes migration and proliferation of BV-2 cells. However, acute inflammatory condition (i.e., high S100A9 doses) causes diminished cell viability; it is uncovered that S100A9 activates TLR-4 and TLR-7 signaling pathways, leading to TNF-α and IL-6 expression, which affect BV-2 cell migration and proliferation in a concentration-dependent manner. Interestingly, the effects of S100A9 are not only inhibited by TNF-α and IL-6 antibodies. The addition of amyloid-ß (Aß) 1-40 peptide resumes the capacities of BV-2 cells to the level of low S100A9 concentrations. Based on these results, we conclude that in contrast to the beneficial effects of low S100A9 dose, high S100A9 concentration leads to impaired mobility and proliferation of immune cells, reflecting neurotoxicity at acute inflammatory conditions. However, the formation of Aß plaques may be a natural mechanism that rescues cells from the proinflammatory and cytotoxic effects of S100A9, especially considering that inflammation is one of the primary causes of AD.

EEG-fest: few-shot based attention network for driver's drowsiness estimation with EEG signals.

The leading factor behind most vehicular accidents is the driver's inattentiveness. To accurately determine driver's drowsiness, Electroencephalography (EEG) has been proven to be a reliable and effective method. Even though previous studies have developed accurate driver's drowsiness detection algorithms, certain challenges still persist, such as (a) limited training sample sizes, (b) detecting anomalous signals, and (c) achieving subject-independent classification. In this paper we propose a novel solution, names as EEG-Fest, which is a generalized few-shot model aimed at addressing the aforementioned limitations. The EEG-Fest has the ability to (a) classify a query sample's level of drowsiness with only a few support sample inputs (b) identify whether a query sample is anomalous signals or not, and (c) perform subject-independent classification. During the evaluation, our proposed EEG-Fest algorithm demonstrates better performance compared to other two conventional EEG algorithms in cross-subject validation.

ArcB orchestrates the quorum-sensing system to regulate type III secretion system 1 in Vibrio parahaemolyticus.

In many Vibrio species, virulence is regulated by quorum sensing, which is regulated by a complex, multichannel, two-component phosphorelay circuit. Through this circuit, sensor kinases transmit sensory information to the phosphotransferase LuxU via a phosphotransfer mechanism, which in turn transmits the signal to the response regulator LuxO. For Vibrio parahaemolyticus, type III secretion system 1 (T3SS1) is required for cytotoxicity, but it is unclear how quorum sensing regulates T3SS1 expression. Herein, we report that a hybrid histidine kinase, ArcB, instead of LuxU, and sensor kinase LuxQ and response regulator LuxO, collectively orchestrate T3SS1 expression in V. parahaemolyticus. Under high oxygen conditions, LuxQ can interact with ArcB directly and phosphorylates the Hpt domain of ArcB. The Hpt domain of ArcB phosphorylates the downstream response regulator LuxO instead of ArcA. LuxO then activates transcription of the T3SS1 gene cluster. Under hypoxic conditions, ArcB autophosphorylates and phosphorylates ArcA, whereas ArcA does not participate in regulating the expression of T3SS1. Our data provides evidence of an alternative regulatory path involving the quorum sensing phosphorelay and adds another layer of understanding about the environmental regulation of gene expression in V. parahaemolyticus.

Dietary Isoquercetin Ameliorates Bone Loss via Restoration of the Gut Microbiota and Lipopolysaccharide-Triggered Inflammatory Status in Ovariectomy Mice.

Osteoporosis is one of the skeletal degenerative diseases accompanied by bone loss and microstructure disruption. Given that the gut-bone signaling axis highly contributes to bone health, here, dietary isoquercetin (IQ) was shown to effectively improve postmenopausal osteoporosis (PMO) in an ovariectomy (OVX) mouse model through the modulation of the gut-bone cross-talk. An in vivo study showed that OVX induced striking disruption of the microbial community, subsequently causing gut leakage and gut barrier dysfunction. As a result, lipopolysaccharide (LPS)-triggered inflammatory cytokines released from the intestine to bone marrow were determined to be associated with bone loss in OVX mice. Long-term dietary IQ effectively improved microbial community and gut barrier function in the OVX mice and thus markedly improved bone loss and host inflammatory status by repressing the NF-κB signaling pathway. An in vitro study further revealed that IQ treatments dose-dependently inhibited LPS-induced inflammation and partly promoted the proliferation and differentiation of osteoblasts. These results provide new evidence that dietary IQ has the potential for osteoporosis treatment.

LncRNA MSTRG.22719.16 mediates the reduction of enoxaparin sodium high-viscosity bone cement-induced thrombosis by targeting the ocu-miR-326-5p/CD40 axis.

OBJECTIVE: Polymethylmethacrylate (PMMA) bone cement promotes the development of local thrombi. Our study found that a novel material, ES-PMMA bone cement, can reduce local thrombosis. We used a simple and reproducible animal model to confirm the reduction in local thrombosis and explored the associated molecular mechanism. METHODS: New Zealand rabbits, which were used to model thrombosis using extracorporeal carotid artery shunts, were divided into the following two groups, with 3 rabbits in each group: the PMMA bone cement group and the ES-PMMA bone cement group. Four hours after modelling, experimental samples, including thrombotic and vascular tissues, were collected. Thrombotic samples from the PMMA group and ES-PMMA group were subjected to lncRNA sequencing, and a lncRNA microarray was used to screen the differentially expressed lncRNAs. The expression of thrombomodulin in endothelial cells was quantified in vascular tissue samples. Differences in the lncRNA expression profiles between the thrombotic samples of the PMMA group and ES-PMMA group were assessed by base-to-base alignment in the intergenic regions of genomes. The lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network was established in light of ceRNA theory. Thrombosis was observed in the PMMA group and ES-PMMA group. RESULTS: The thrombotic weight was 0.00706 ± 0.00136 g/cm in the PMMA group and 0.00551 ± 0.00115 g/cm in the ES-PMMA group. Quantitative real-time polymerase chain reaction (RT-q-CR) and Western blotting revealed that the expression of CD40, which can regulate thrombosis in vascular endothelial cells, was significantly lower in the ES-PMMA group than in the PMMA group. High-throughput sequencing was used to identify 111 lncRNAs with lower expression in the ES-PMMA group than in the PMMA group. Through bioinformatics investigation, lncRNA MSTRG22719.16/ocu-miR-326-5p/CD40 binding sites were selected. Fluorescent in situ RNA hybridization (FISH) was performed to verify the lower expression of lncRNA MSTRG.22719.16 in vascular tissues from the ES-PMMA group. A dual-luciferase reporter gene assay was applied to verify that ocu-miR-326-5p binds the CD40 3'-UTR and targets lncRNA MSTRG.22719.16. CONCLUSION: Compared with PMMA bone cement, ES-PMMA bone cement can reduce thrombosis through the lncRNA MSTRG.22719.16/ocu-miR-326-5p/CD40 axis.

Discovery of a novel small molecule with efficacy in protecting against inflammation in vitro and in vivo by enhancing macrophages activation.

Immune response and inflammation highly contribute to many metabolic syndromes such as inflammatory bowel disease (IBD), ageing and cancer with disruption of host metabolic homeostasis and the gut microbiome. Icariin-1 (GH01), a small-molecule flavonoid derived from Epimedium, has been shown to protect against systemic inflammation. However, the molecular mechanisms by which GH01 ameliorates ulcerative colitis via regulation of microbiota-mediated macrophages polarization remain elusive. In this study, we found that GH01 effectively ameliorated dextran sulfate sodium (DSS)-induced colitis symptoms in mice. Disruption of intestinal barrier function, commensal microbiota and its metabolites were also significantly restored by GH01 in a dose-dependent manner. Of note, we also found that GH01 enhanced phagocytic ability of macrophages and switched macrophage phenotype from M1 to M2 both in vitro and in vivo. Such macrophage polarization was highly associated with intestinal barrier integrity and the gut microbial community. Consequently, GH01 exhibited strong anti-inflammatory capacity by inhibiting TLR4 and NF-κB pathways and proinflammatory factors (IL-6). These findings suggested that GH01 might be a potential nutritional intervention strategy for IBD treatment with the gut microbial community-meditated macrophage as the therapeutic targets.